Transient tumor exposure induces persistent functional defects in memory CD8+ T cells
Abstract
Memory CD8 + T cells generated during acute infections exhibit enhanced effector functions upon reactivation. However, persistent antigen exposure, such as in cancer, can impair their functionality. In this study, we compared memory CD8 + T cells generated following tumor rejection (Tum-CD8 + ) with those arising from an acute viral infection (Vir-CD8 + ). Using vaccinia virus and EL4 tumor models expressing the same antigen, we found that Tum-CD8 + cells displayed a distinct phenotype, including sustained expression of inhibitory receptors (PD-1, TIM-3), altered integrin expression, and reduced production of IFNγ and TNF. Despite retaining cytotoxic activity, their protective capacity was compromised, even after viral recall. Transcriptomic and functional analyses revealed that transient tumor exposure imprints a stable, exhaustion-like program on memory CD8 + T cells. These findings highlight how suboptimal priming conditions during tumor challenge durably shape memory T cell responses.
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BibTeX
@article{laubreton2026transient,
title = {{Transient tumor exposure induces persistent functional defects in memory CD8+ T cells}},
author = {Daphné Laubreton and Margaux Prieux and Sophia Djebali and Maxence Dubois and Simon de Bernard and Olivier Gandrillon and Christophe Arpin and Jacqueline Marvel},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.115556},
url = {https://hal.science/hal-05845497v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Transient tumor exposure induces persistent functional defects in memory CD8+ T cells
AU - Daphné Laubreton
AU - Margaux Prieux
AU - Sophia Djebali
AU - Maxence Dubois
AU - Simon de Bernard
AU - Olivier Gandrillon
AU - Christophe Arpin
AU - Jacqueline Marvel
PY - 2026
DA - 2026/10/30
JO - iScience
DO - 10.1016/j.isci.2026.115556
UR - https://hal.science/hal-05845497v1
AB - Memory CD8 + T cells generated during acute infections exhibit enhanced effector functions upon reactivation. However, persistent antigen exposure, such as in cancer, can impair their functionality. In this study, we compared memory CD8 + T cells generated following tumor rejection (Tum-CD8 + ) with those arising from an acute viral infection (Vir-CD8 + ). Using vaccinia virus and EL4 tumor models expressing the same antigen, we found that Tum-CD8 + cells displayed a distinct phenotype, including sustained expression of inhibitory receptors (PD-1, TIM-3), altered integrin expression, and reduced production of IFNγ and TNF. Despite retaining cytotoxic activity, their protective capacity was compromised, even after viral recall. Transcriptomic and functional analyses revealed that transient tumor exposure imprints a stable, exhaustion-like program on memory CD8 + T cells. These findings highlight how suboptimal priming conditions during tumor challenge durably shape memory T cell responses.
SN - 2589-0042
ER -